evaluation of clinical efficacy and immunologic response after il-2 therapy in hcv-related vasculitis patients

Conditions: Cryoglobulinemia Vasculitis

Summary: a systemic vasculitis is found in 5 to 10% of hcv infected patients with mixed cryoglobulinemia (mc). it mainly involves the skin, peripheral nerve and the kidney and may be life threatening. twenty to 30% of hcv-mc vasculitis patients are resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors) and still have an active disease. thus, new therapeutic approaches are necessary in such patients. we recently described a regulatory t cell (treg) deficiency in hcv-related vasculitis patients. immunomodulatory effects of interleukin-2 (il-2) are well established, notably the preferential expansion of treg able to suppress inflammatory responses mediated by cd4+ and cd8+ t cells.

a systemic vasculitis is found in 5 to 10% of hcv infected patients with mixed cryoglobulinemia (mc). it mainly involves the skin, peripheral nerve and the kidney and may be life threatening (15% of death). twenty to 30% of hcv-mc vasculitis patients are resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors) and still have an active disease. an antiviral therapy with peg-interféron is generally prescribed to control vasculitis lesions and to slow down the hepatic fibrosis progression. thus, new therapeutic approaches are necessary in such patients. we recently described a cd4+ cd25+ regulatory t cell (treg) deficiency in hcv-related vasculitis patients. immunomodulatory effects of interleukin-2 (il-2) are well established, notably the preferential expansion of treg able to suppress inflammatory responses mediated by cd4+ and cd8+ t cells. objective : to evaluate the cellular immune response after il-2 therapy in hcv-mc vasculitis patients, resistant to conventional therapy. methods : this is an open prospective phase i/ii trial. four cycle of subcutaneous il-2 therapy (3 millions iu/day from day 1 to 5 every 21 days will be carried out at w1, w3, w6, and w9). the first cure will be carried out with half-dose of il-2 (1.5 millions iu/day) in the hospital. if the tolerance is satisfactory, the later cures will be done ambulatory. all patients will be followed after il-2 therapy (s11 to s37). end points : 1. clinical tolerance: absence of vasculitis flare during and after il-2 therapy. 2. immunologic follow-up of treg and of hcv cellular immune response before, during and after il-2 therapy. 3. clinical efficacy: follow-up of clinical manifestations of hcv-mc vasculitis during and after il-2 therapy. schedule : duration of patients' inclusion period is estimated 18 months. duration of therapy and follow-up is estimated 9 months. analysis of data will last 7 months. overall duration: 34 months

Eligibility criteria:
inclusion criteria: 1. hcv+ patients with cryoglobulinemia vasculitis 2. resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors). 3. vasculitis is defined according to international criteria: chronic hcv infection (hcv rna+), 4. serum cryoglobulin superior or equal to 0.05g/l in at least two determinations, 5. presence of the triad purpura-arthralgia-asthenia and/or biopsy proven vasculitis (kidney, nerve or skin).

Keywords: hcv+ cryoglobulinemia vasculitis il-2 treatment safety and efficacy